การวิจัยและพัฒนาผลิตภัณฑ์เสริมสุขภาพจากผักชีลาวเพื่อป้องกันโรคไขมันพอกตับ

บทคัดย่อ

Fatty liver disease (FLD) includes non-alcoholic fatty liver disease and alcohol-induced fatty liver disease (AFLD) are health-threatening diseases of the global population. The incidence of NAFLD in the western population is about 20-30% and 2-3% of these NAFLD patients develop the disease to cirrhosis and liver cancer. Chlorogenic acid (CGA) and ellagic acid (EA) are abundant in dill (Anethum graveolens) and hypothesized as the main active compounds due to their potential to lower lipid, cholesterol, and triglyceride levels with anti-oxidation and anti-inflammatory effects. This study aimed to develop an oral health supplement product from dill extract as self-emulsifying drug delivery system (SEDDS) in pharmaceutical technology and to study the potential of dill extract in prevention of NAFLD in human hepatocellular carcinoma HepG2 model. Tertiary phase diagrams were employed to determine the appropriate ratio of surfactants, cosurfactants, and oils in SEDDS of the dill extract by using water titration method. And then the solid form of SEDDS of the dill extract were developed by physical mixing with absorbents or solid carriers. The results revealed that Kolliphor EL and Transcutol as surfactants, and propylene glycol as a cosurfactant coupled with a mixture of medium chain triglyceride (MCT oil) and oleic acid provided the SEDDS possessed the particle size of 68.16?1.15 nm, Polydispersity Index (PDI) of 0.135?0.019, and zeta potential of -3.93?0.51 mV. Neusilin? US2 was selected as the solid carrier to develop the solid form of SEDDS of dill extract. The characteristic of the SEDDS solid form was a dry powder. Neusilin? was coated with the dill extract as shown under SEM. Flowability of the SEDDS solid form was excellent considering the angle of repose with the lowest compressibility index. The thermal analysis indicated that the SEDDS of dill extract was fully bound to the adsorbent, resulting in the same thermogram as the adsorbent. The X-ray powder diffraction pattern assured amorphous form of the SEDDS solid, which was suitable for development of an oral formulation to further study dissolution rate and stability. The study of the potential of dill extract in preventing NAFLD in HepG2 cells showed that a 1:1 mixture of oleic acid (OA) and palmitic acid (PA) successfully induced NAFLD in HepG2 cells by inducing cellular lipid accumulation and modifying expression profiles of fatty acid biosynthesis-related genes, such as PPAR?, PPAR?, SREBP-1a, SREBP-1c, ACC, ACOX, and FAS, in a consistent pattern with NAFLD. The dill extract, CGA, and EA showed the potential to normalize the expression of these genes comparably to the standard drug fenofibrate (Feno), with the advantage of not affecting ALT and ROS levels. Moreover, the dill extracts, CGA, and EA upregulated the expression levels of oxidative stress-regulated genes, namely CAT, SOD1, and SOD2 and thereby downregulated the expression of inflammatory genes, namely TNF? and IL-8, to the level comparable to the control. Concerning the effect on CYPs, the dill extracts, CGA, and EA had advantages over Feno in suppressing the expression of CYP2E1 and CYP4A11, isoforms involved in oxidative stress in NAFLD and normalizing the CYP3A4 expression level. Nevertheless, impacts of the dill extract, CGA, and EA against the expression profiles of multiple CYPs isoforms are required further study in vivo to confirm their safety, particularly herb-drug interactions and to serve as a basis for determining the contraindications/precautions of products containing the dill extract, CGA, and EA prior to clinical study. In conclusion, the dill extract is a highly potential herbal extract for development as an oral alternative health supplement and study on its efficacy for NAFLD therapy and risks of drug interactions/adverse reactions in experimental animals in the future.

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